Supplementary Material for: Tenofovir Is Superior to Entecavir on Tertiary Prevention for BCLC Stage 0/A Hepatocellular Carcinoma after Curative Resection

<b><i>Background:</i></b> It is unclear whether entecavir (ETV) and tenofovir disoproxil fumarate (TDF) have different effects on hepatocellular carcinoma (HCC) recurrence and death in patients receiving curative hepatectomy for hepatitis B virus (HBV)-related HCC. <b><i>Aims:</i></b> The aim of this study was to compare the long-term efficacy of ETV and TDF in HCC recurrence and overall survival (OS) of patients after curative hepatectomy. <b><i>Methods:</i></b> From January 2010 to December 2019, 20,572 patients with HCC who received hepatectomy were screened for study eligibility. Finally, a total of 219 consecutive patients treated with ETV (<i>n</i> = 146) or TDF (<i>n</i> = 73) after curative hepatectomy for HBV-related HCC of Barcelona Clinic Liver Cancer stage 0 or A were analyzed by propensity score matching (PSM) (2:1) analysis and competing risk analysis. HCC recurrence and OS of patients were compared between ETV and TDF groups. <b><i>Result:</i></b> After a median follow-up of 52.2 months, 81 patients (37.0%) had HCC recurrence, 33 (15.1%) died, and 5 (2.3%) received liver transplantation. TDF therapy was an independent protective factor for HCC recurrence compared with ETV therapy (HR, 1.687; 95% CI, 1.027–2.770, <i>p</i> = 0.039); however, no difference in the risk of death or liver transplantation. Results were similar in competing risk analysis. We further found that TDF therapy was significantly associated with a lower risk of late recurrence (HR, 4.705; 95% CI, 1.763–12.558, <i>p</i> = 0.002), but not in early recurrence. <b><i>Conclusions:</i></b> TDF therapy is associated with a significantly lower risk of HCC recurrence, especially of late recurrence, than ETV therapy among patients who undergo curative hepatectomy for HBV-related early-stage HCC.

<b><i>背景：</i></b> 目前尚不明确恩替卡韦（entecavir, ETV）与富马酸替诺福韦二吡呋酯（tenofovir disoproxil fumarate, TDF）在接受根治性肝切除术治疗的乙型肝炎病毒（hepatitis B virus, HBV）相关肝细胞癌（hepatocellular carcinoma, HCC）患者中，对肿瘤复发及死亡的影响是否存在差异。<b><i>研究目的：</i></b> 本研究旨在对比恩替卡韦与富马酸替诺福韦二吡呋酯在HBV相关HCC患者根治性肝切除术后，对肿瘤复发及总生存期（overall survival, OS）的长期疗效。<b><i>方法：</i></b> 2010年1月至2019年12月，共对20572例接受肝切除术的HCC患者进行研究资格筛选。最终纳入219例连续性患者，均为巴塞罗那临床肝癌（Barcelona Clinic Liver Cancer, BCLC）分期0期或A期的HBV相关HCC患者，且在根治性肝切除术后分别接受恩替卡韦（n=146）或富马酸替诺福韦二吡呋酯（n=73）抗病毒治疗。本研究通过倾向得分匹配（propensity score matching, PSM）（2:1）分析及竞争风险分析对上述患者进行回顾性研究，并对比两组患者的HCC复发情况与总生存期。<b><i>结果：</i></b> 中位随访时长为52.2个月，期间81例（37.0%）患者出现HCC复发，33例（15.1%）死亡，5例（2.3%）接受肝移植。与恩替卡韦治疗组相比，富马酸替诺福韦二吡呋酯治疗是HCC复发的独立保护因素（风险比HR=1.687；95%置信区间CI：1.027~2.770，P=0.039）；但两组患者的死亡或肝移植风险无显著差异。竞争风险分析得到了一致的结果。进一步分析显示，富马酸替诺福韦二吡呋酯治疗与更低的晚期复发风险显著相关（HR=4.705；95%CI：1.763~12.558，P=0.002），但对早期复发无显著影响。<b><i>结论：</i></b> 对于接受根治性肝切除术治疗的HBV相关早期HCC患者，富马酸替诺福韦二吡呋酯治疗相较恩替卡韦治疗，可显著降低HCC复发风险，尤其是晚期复发风险。